Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug (AED) for focal (partial-onset) seizures (FS). Psychiatric and suicidality-related treatment-emergent adverse events (TEAEs) have been reported to be associated with AED treatment, and some were observed during clinical trials of ESL in adults. Here, we evaluate the occurrence of psychiatric TEAEs and suicidality in clinical trials of ESL for FS in children. Methods: Pooled safety data from subjects aged 4–17 yrs in Studies BIA-2093-208 and -305 were analyzed. Both trials were randomized, double-blind, placebo-controlled studies of adjunctive ESL in children with FS refractory to 1–2 AEDs. Study 208-Part 1 was a 12-week, Phase II study in subjects aged 6–16 yrs, with a target ESL dose of 30 mg/kg/day. Study 305-Part 1 was an 18-week, Phase III study in subjects aged 2–18 yrs, with a target ESL dose of 20 mg/kg/day. Subjects could continue into a 1-yr uncontrolled, open-label extension (OLE) (Part 2); and potentially into further OLEs: Study 208, Part 3 (2 yrs); Study 305, Parts 3–4 (1 yr each), Part 5 (2 yrs). For this analysis, we aggregated incidences of investigator-reported TEAEs, serious adverse events (SAEs), and TEAEs leading to discontinuation in the ‘psychiatric disorders’ category. Suicidal-ideation/behavior medically-significant events (MSEs) included incidences of investigator-reported TEAEs of ‘suicide attempt’ or ‘completed suicide’, as well as TEAEs in the ‘suicide’ Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Results: The analysis population (subjects who received =1 dose of ESL) included 362 subjects (ESL, n = 202; placebo, n = 160) for the controlled study periods and 337 for the OLE (Part 2). In the ESL group, mean age was 11.1 yrs (SD: 3.39), with most subjects aged =7 yrs (4–6 yrs, 11.4%; 7–11 yrs, 41.6%; 12–17 yrs, 47.0%). Psychiatric TEAEs: agitation (ESL, n = 5 [2.5%]; placebo, n = 1 [0.6%]) and insomnia (ESL, n = 2 [1.0%]; placebo, n = 4 [2.5%]) occurred in =2% of subjects taking ESL or placebo. Aggression was reported in one patient taking ESL in each of the controlled (0.5%) and uncontrolled (1-yr OLE: 0.3%; post–1-yr OLE: 0.6%) study periods. An SAE of ‘conduct disorder’ was reported for one subject during the 1-yr OLE (0.3%), and ‘abnormal behavior’ led to treatment discontinuation in two subjects (0.6%) during the same period. No psychiatric SAEs or TEAEs leading to discontinuation were reported during the post 1-yr OLE. Suicidal-ideation/behavior MSEs: no suicidal-ideation/behavior MSEs were reported during the double-blind or OLE study periods. There were no reports of Major Depressive Disorder during any study period. Conclusions: Psychiatric TEAEs were uncommon, and there were no reports of suicidal ideation or behavior during double-blind and OL studies of adjunctive ESL in children (aged 4–17 years) with FS. Funding: Studies sponsored by BIAL; analyses funded by Sunovion Pharmaceuticals Inc.